Triptans in prevention of menstrual migraine: a systematic review with meta-analysis

Hu Y, Guan X, Fan L, Jin L

CRD summary

The authors concluded that triptans were an effective short-term prophylactic treatment for menstrual migraines. Considering migraine frequency, severity and adverse events, frovatriptan 2.5mg twice daily and zolmitriptan 2.5mg three times daily were the most preferable regimens. The conclusion regarding the effectiveness of triptans seems reliable; the recommendations for further research were justified.

Authors' objectives

To evaluate the efficacy and tolerability of triptans in the prevention of menstrual migraine.

Searching

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to October 2012 with no language restrictions. Search terms were reported. Reference lists of identified studies were handsearched.

Study selection

Randomised controlled trials that compared the efficacy and tolerability of triptans versus placebo in the prevention of menstrual migraine were eligible for inclusion. The primary outcome of interest was the proportion of patients free from menstrual migraine per peri-menstrual period; secondary outcomes included the characteristics of menstrual migraine. Menstrual migraine had to be diagnosed using criteria developed by the International Headache Society or other definitions that conformed in general to these criteria.

Most of the included trials were conducted in USA. The mean age of participants ranged from 36 to 38 years. Types of triptan administered included frovatriptan, naratriptan and zolmitriptan; doses ranged from 1mg to 2.5mg (administered once, twice or three times daily) and were administered for five to seven days at two to three days before menstrual migraine onset. Five out of the six trials used International Headache Society criteria to diagnose menstrual migraine. Most trials evaluated the primary outcome of interest; other outcomes included use of rescue medication and severity, duration and symptoms related to menstrual migraine.

Two reviewers independently selected studies for inclusion; any disagreements were resolved by discussion with a third reviewer.

Assessment of study quality

Study quality was assessed using the Oxford Quality Scale to allocate scores from 0 (lowest quality) to 5 (highest quality). Criteria were used to assess risk of bias associated with randomisation methods, allocation concealment and blinding.

The authors did not report how many reviewers undertook the quality assessment.

Data extraction

Two reviewers independently extracted data on the outcomes (number of events) to calculate risk ratios with 95% confidence intervals (CI). Data appeared to have been extracted from intention-to-treat analyses. Any disagreements in data extraction were resolved by discussion with a third reviewer.

Methods of synthesis

Risk ratios and 95% CI were pooled using fixed-effect models. Statistical heterogeneity between the trials was assessed using the Ι² and Q statistics. The numbers needed to treat to benefit (NNTB) or harm (NNTH) and 95% CI were calculated.

Results of the review

Six double-blind randomised controlled trials (1,999 participants) were included in the review; one of these had a crossover design (506 participants). Four trials scored 5 out of 5 on quality. Methodological limitations for the other two trials related to lack of reporting for randomisation methods and blinding. No studies were rated as having a high risk of bias.

Compared with placebo, the proportion of patients free from menstrual migraine was statistically significantly increased among those taking frovatriptan in doses of 2.5mg once daily (RR 1.48, 95% CI 1.27 to 1.72; two trials; Ι²=0%) and 2.5mg twice daily (RR 1.82, 95% CI 1.58 to 2.09; two trials; Ι²=0%). The NNTB for the comparison involving the 2.5mg once daily regimen was 7.22 (95% CI 5.25 to 11.54). The NNTB for the comparison involving the 2.5mg twice daily regimen was 3.90 (95% CI 3.23 to 4.93).

A similar result was shown with the use of naratriptan in a dose of 1mg twice daily (RR 1.48, 95% 1.20 to 1.83; three trials; Ι²=14.5%). This comparison resulted in a NNTB of 7.98 (95% CI 5.24 to 16.71). One trial compared naratriptan 2.5mg twice daily with placebo and found no statistically significant differences in overall menstrual migraine rates or number of menstrual migraine days between the groups.

One trial (244 participants) compared zolmitriptan (2.5mg twice daily or three times daily) with placebo and found that both regimens had superior efficacy to placebo as demonstrated by a 50% or more reduction in the frequency of menstrual migraines and the mean number of breakthrough migraines per menstrual cycle. In the comparisons with placebo, the NNTB for the proportion of patients free from menstrual migraine per menstrual cycle was 4.98 (95% CI 3.26 to 10.57) for the 2.5mg twice daily regimen and 2.52 (95% CI 1.95 to 3.58) for the 2.5mg three times daily regimen.

The review question and inclusion criteria were defined clearly. Relevant sources of data were accessed. There were no language restrictions. Limited searching for unpublished/grey literature meant that relevant studies may have been missed. Efforts were taken during study selection and data extraction to minimise any reviewer error or bias; this was not reported for the process of quality assessment. Quality assessment criteria were suitable and most trials were found to be of good quality. Quality issues that sometimes occur with trials were not assessed (such as comparability of groups at baseline and completeness of outcome reporting).

Study details were presented. Methods of synthesis were appropriate. The authors acknowledged that the results were limited by the small number of trials included; these tested only three drugs in two difference doses. The authors stated that the inadequate numbers of participants and events meant that no firm conclusions could be made about differences between different drugs/doses.

The authors' conclusion regarding the overall effectiveness of triptans seems reliable; the paucity of the evidence supports their recommendations for further research.

Implications of the review for practice and research

Practice: The authors stated that frequency and dose of triptans should be adjusted in the treatment of menstrual migraines because frovatriptan has a long half-life (26 hours) and zolmitriptan has a short half-life (3 hours). Women with menstrual migraines should only become candidates for short-term preventative therapy with a triptan if they do not achieve adequate relief from acute therapies; this should particularly be the case in those who experience regular menstrual migraines that cause significant disability.

Research: The authors stated that studies with longer durations were required to further investigate safety and tolerability of triptans in the treatment of menstrual migraines. Future studies should monitor migraine attacks during menses and establish the differences between different triptans and doses and between triptans and alternative drugs such as estradiol or topiramate.

Funding

National Science Foundation of China; Fundamental Research Funds for the Central Universities.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.